1-(3-chloropropyl)-2-phenyl-1H-imidazole | 126036-05-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(3-chloropropyl)-2-phenyl-1H-imidazole
• 英文别名: 1-(3-chloropropyl)-1H-2-phenylimidazole；1-(3-chloropropyl)-2-phenylimidazole
• CAS: 126036-05-3
• 化学式: C₁₂H₁₃ClN₂
• mdl: MFCD12785004
• 分子量: 220.702
• InChiKey: YLICGSPHZQJKPH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  17.8
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-(3-chloropropyl)-2-phenyl-1H-imidazole 在 sodium hydride 、 potassium carbonate 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 14.5h， 生成 1-(cyclopentylmethyl)-6-fluoro-2-(2-fluorophenyl)-3-(1-(3-(2-phenyl-1H-imidazol-1-yl)propyl) piperidin-4-yl)-2,3-dihydroquinazolin-4(1H)-one
  参考文献：
  名称：

  Discovery of Novel KRAS-PDEδ Inhibitors by Fragment-Based Drug Design

  摘要：

  [Graphics]Targeting KRAS-PDE delta protein-protein interactions with small molecules represents a promising opportunity for developing novel antitumor agents. However, current KRAS-PDE delta inhibitors are limited by poor cellular antitumor potency and the druggability of the target remains to be validated by new inhibitors. To tackle these challenges, herein, novel, highly potent KRAS-PDE delta inhibitors were identified by fragment-based drug design, providing promising lead compounds or chemical probes for investigating the biological functions and druggability of KRAS-PDE delta interaction.

  DOI：

  10.1021/acs.jmedchem.8b00057
• 作为产物：
  描述：

  2-苯基咪唑 在 氯化亚砜 、 caesium carbonate 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 14.0h， 生成 1-(3-chloropropyl)-2-phenyl-1H-imidazole
  参考文献：
  名称：

  Discovery of Novel KRAS-PDEδ Inhibitors by Fragment-Based Drug Design

  摘要：

  [Graphics]Targeting KRAS-PDE delta protein-protein interactions with small molecules represents a promising opportunity for developing novel antitumor agents. However, current KRAS-PDE delta inhibitors are limited by poor cellular antitumor potency and the druggability of the target remains to be validated by new inhibitors. To tackle these challenges, herein, novel, highly potent KRAS-PDE delta inhibitors were identified by fragment-based drug design, providing promising lead compounds or chemical probes for investigating the biological functions and druggability of KRAS-PDE delta interaction.

  DOI：

  10.1021/acs.jmedchem.8b00057

文献信息

• 二氢喹唑啉酮类衍生物及其制备方法与应用
  申请人：中国人民解放军第二军医大学

  公开号：CN108276391A

  公开（公告）日：2018-07-13

  本发明涉及医药技术领域，具体涉及具有以下化学结构通式的一类新的二氢喹唑啉酮类衍生物及其药学上可接受的盐类：药理实验表明，本发明所述的衍生物或盐，对KRAS‑PDEδ蛋白相互作用具有很强的抑制活性，而且具有较强的体外抗肿瘤活性。本发明还提供了上述衍生物及其药学上可接受的盐的制备方法，以及在制备KRAS‑PDEδ抑制剂和抗肿瘤药物中的应用。
• Stille Cross-Coupling Reactions with Tin Reagents Supported on Ionic Liquids
  作者：Phuoc Dien Pham、Jürgen Vitz、Cécile Chamignon、Arnaud Martel、Stéphanie Legoupy

  DOI：10.1002/ejoc.200900177

  日期：2009.7

  ionic-liquid-supported tin reagents were synthesized and used in Stille cross-coupling reactions. High yields of biaryls were obtained under low-temperature, solvent-free, ligand-free conditions, with simple purification techniques. Moreover, the tin compound could be recycled up to five times without significant loss of reactivity. An expanded catalytic cycle for the Stille cross coupling reaction is proposed in

  合成了新的离子液体负载锡试剂并用于斯蒂勒交叉偶联反应。在低温、无溶剂、无配体的条件下，通过简单的纯化技术获得了高收率的联芳基化合物。此外，锡化合物最多可循环使用五次，而不会显着降低反应性。为了解释在某些反应条件下形成的副产物，提出了 Stille 交叉偶联反应的扩展催化循环。 (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
• Structure-activity relationship of N-[2-(dimethylamino)-6-[3-(5-methyl-4-phenyl-1H-imidazol-1-yl)propoxy]phenyl]-N'-pentylurea and analogs. Novel potent inhibitors of acyl-CoA:cholesterol O-acyltransferase with antiatherosclerotic activity
  作者：Teiji Kimura、Yasutaka Takase、Kenji Hayashi、Hiroshi Tanaka、Issei Ohtsuka、Takao Saeki、Motoji Kogushi、Toshie Yamada、Tohru Fujimori

  DOI：10.1021/jm00063a013

  日期：1993.5

  urea (4), a novel, potent, and systemically bioavailable inhibitor of ACAT (acylCoA:cholesterol O-acyltransferase). The structure-activity relationships (SARs) of this lead compound 4 were investigated by systematic modification of four regions in the molecule. The compounds prepared in this study were tested for in vitro inhibitory activity toward both aortic and intestinal ACATs, and selected compounds

  我们发现了一种新颖，有效的N-丁基-N'-[2-（二甲基氨基）-6- [3-（4-苯基-1H-咪唑-1-基）丙氧基]苯基]脲（4）全身可利用的ACAT抑制剂（酰基CoA：胆固醇O-酰基转移酶）。通过系统修饰分子中的四个区域，研究了该先导化合物4的构效关系（SAR）。测试了本研究中制备的化合物对主动脉和肠道ACAT的体外抑制活性，并进一步测试了所选化合物的体内降胆固醇活性。这些研究不仅导致发现了N- [2-（二甲基氨基）-6- [3-（5-甲基-4-苯基-1H-咪唑-1-基）丙氧基]苯基] -N'-戊脲（ 24），口服后具有有效的活性和适度的血浆水平，而且还揭示了每个修饰区域的SAR。进一步选择了四种化合物（4、13、14、24）来测试体内抗动脉粥样硬化活性。4、13和24将动脉粥样硬化斑块的形成减少到对照面积的38-45％，而14则没有明显的抗动脉粥样硬化作用。
• Ligand exchange between cyanocuprates and allylic stannanes: a novel, direct route to allylic cuprates possessing remarkable reactivity and stability
  作者：Bruce H. Lipshutz、Robert Crow、Stuart H. Dimock、Edmund L. Ellsworth、Robin A. J. Smith、James R. Behling

  DOI：10.1021/ja00166a067

  日期：1990.5